To inform clinical decision-making for persons with multiple chronic conditions (MCC), we must compare the effects of treatments across conditions. In this study, we go beyond the question of comparative benefit of treatments for a single condition on single condition-specific outcomes to begin exploring the comparative effectiveness of treatments across multiple conditions on multiple universal health outcomes (e.g. function, symptoms, and survival) that are meaningful to patients and that are affected by all health conditions. Multiple universal outcomes are important to explore because treatments may affect outcomes differently and older adults with MCC vary in their health outcome priorities. While complex, this line of investigation is responsive to the RFA-AG-13-003 and of utmost relevance for older individuals with MCC. The project builds on recent work in which we have: 1) identified a set of universal health outcomes; 2) determined the effect of several common conditions on these outcomes; 3) developed a method for determining the % contribution to death of co-occurring conditions; 4) identified the most common pairs of competing conditions; and 5) determined the effects of treatment for one condition on a potentially competing condition. In conducting this work, we have come to appreciate the methodological challenges that help explain the dearth of research in this area despite its clinical importance. The proposed methodology builds on our recent work in adapting joint modeling of longitudinal outcomes and developing the longitudinal extension of the average attributable fraction. Using innovative analytical methods, the Specific Aims are to: 1) estimate the effect of the 9 most commonly used guideline recommended medication classes for a set of common and morbid chronic conditions on 5 universal health outcomes; and 2) estimate the percent contribution of each medication to each universal outcome. Participants will be members of the large, well-characterized, nationally representative Medicare Current Beneficiary Survey (MCBS) cohort who have e 2 of the 9 study conditions. From a clinical perspective, this line of investigation eventually will allow an evidence-based approach to polypharmacy for patients with MCC by identifying medications with the best overall benefits. Results will inform future studies by introducing new methods, identifying promising treatments to compare in persons with MCC, and determining effect size and power estimates. Because MCBS represents the national older population with variable combinations of MCC, results will provide a population-level estimate of the relative effects of the study medications.